Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)Phase 2PRIZMNCT06402123
A Phase 2b Study of Zagociguat in Patients With MELAS
A Phase 2 study testing zagociguat 15mg and zagociguat 30mg in people with Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome), run by Tisento Therapeutics at 20 sites in 6 countries.
Trial summary
PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)
- What is being tested?
- zagociguat 15mg and zagociguat 30mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 10 Sep 2024to 29 Jun 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed consent form.
- 18 to 75 years of age.
- Diagnosed with MELAS based on the presence of each of the following criteria:
- A documented pathogenic variant in a mitochondrial DNA (mtDNA) gene.
- History of one or more stroke-like episodes (SLEs) with magnetic resonance imaging (MRI) findings consistent with stroke-like lesions.
- Scores below normal average on the iDSST and GMLT.
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- Reports fatigue due to MELAS.
- Can complete at least 1 sit-to-stand in the 30-second test interval.
- Completes all at-home weekly activities independently during the Screening Period (caregiver may help set up device/app, log-in, etc.).
- Other criteria per the protocol.
Who cannot join
- Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg.
- Orthostatic hypotension when measured after standing from a semi-recumbent/supine position.
- Active cancer significant enough to confound the results of this study.
- Severe gastrointestinal dysmotility that may impact participation.
- Recent history (within last 6 months) of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis condition(s), or significant, nontraumatic bleeding episodes.
- History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation.
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- Current use of prohibited medication (reviewed by investigator).
- Any medical or other condition that the investigator thinks would preclude study participation.
- Other exclusion criteria per protocol.
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States10 sites
Akron Children's Hospital
Akron, Ohio, 44308
Rare Disease Research
Atlanta, Georgia, 30329
Children's Hospital of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Baylor College of Medicine
Houston, Texas, 77030
University of Texas Medical School at Houston
Houston, Texas, 77030
UC San Diego - Altman Clinical and Translational Research Institute
La Jolla, California, 92037
Columbia University Irving Medical Center
New York, New York, 10027
Mount Sinai - Ichan School of Medicine
New York, New York, 10029
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Australia2 sites
Royal Melbourne Hospital
Melbourne, Victoria, 3052
Neuroscience Research Australia
Sydney, New South Wales, NSW 2031
Canada2 sites
McMaster University Medical Center
Hamilton, Ontario, L8N 3Z5
Shared Health/University of Manitoba
Winnipeg, Manitoba, R3A1R9
Germany2 sites
University Hospital Bonn
Bonn, 53127
Ludwig-Maximilians-University of Munich
Munich, 80336
Italy2 sites
Neurologic Institute Carlo Besta of Milan
Milan, 20133
Fondazione Policlinico Universitario Agostino Gemelli
Roma, 00168
United Kingdom2 sites
UCL Queen Square Institute of Neurology
London, London, WC1N 3BG
Newcastle University
Newcastle upon Tyne, NE14LP
About this study
Official title: Phase 2b Randomized, Double-blind, Placebo-controlled Crossover Study Evaluating the Efficacy and Safety of Zagociguat in Participants With MELAS (PRIZM)
PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS.
Read the detailed description
The goal of this clinical trial is to learn about the effectiveness of zagociguat in patients with MELAS. The main questions it aims to answer are:
- Does zagociguat improve fatigue in patients with MELAS?
- Does zagociguat improve cognitive performance in patients with MELAS?
- What is the safety and tolerability profile of zagociguat?
The PRIZM study is evaluating 2 dose levels of zagociguat in a crossover design consisting of two 12-week treatment periods separated by a 4-week washout. Patients will be screened and if eligible, randomly assigned either to receive placebo in period 1 followed by active drug in period 2 OR to receive active drug in period 1 followed by placebo in period 2. Study medication is a once daily oral tablet and will be provided at the clinic and/or shipped to the participant's home. Clinic visits will occur at screening and Week 1 and Week 12 of each treatment period. Visits at Week 4 and Week 8 of both crossover periods will either be in clinic or optionally at the participant's home. Study assessments will be conducted weekly on a phone app and a separate tablet and additional assessments will be conducted during visits. Patients who complete the study will be eligible for an open label extension study.
- Being tested
- zagociguat 15mg, zagociguat 30mg, Placebo
- Keywords
- MELAS
- Medical subject headings
- Mitochondrial encephalopathy, Acidosis, Lactic, MELAS Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zagociguat 15mgDrug
Also called IW-6463, CY6463
Once-daily oral tablets
zagociguat 30mgDrug
Also called IW-6463, CY6463
Once-daily oral tablets
PlaceboDrug
Once-daily oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Placebo then Zagociguat 15mg | Experimental | Participants first receive placebo once a day for 12 weeks. Then after a 4 week washout, they receive zagociguat 15 mg once a day for 12 weeks. Receives: Drug: zagociguat 15mg; Drug: Placebo |
| Zagociguat 15mg then Placebo | Experimental | Participants first receive zagociguat 15 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks. Receives: Drug: zagociguat 15mg; Drug: Placebo |
| Placebo then Zagociguat 30mg | Experimental | Participants first receive placebo once a day for 12 weeks. Then after a 4-week washout, they receive zagociguat 30 mg once a day for 12 weeks. Receives: Drug: zagociguat 30mg; Drug: Placebo |
| Zagociguat 30mg then Placebo | Experimental | Participants first receive zagociguat 30 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks. Receives: Drug: zagociguat 30mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
• PROMIS Fatigue MELAS Short Form scores• Groton Maze Learning Test scores • International Digit Symbol Substitution Test scores
These measures are a patient reported questionnaire on MELAS-specific fatigue and 2 cognitive performance tests. These 3 outcome measures will be combined using a global statistical test.
Measured: Weeks 9 through 12 of each treatment period
Incidence of Treatment-emergent Adverse Events (TEAEs)
TEAEs are any untoward event that may or may not be related to study medication.
Measured: Weeks 1 through washout for treatment period 1 and Weeks 1 through follow-up for treatment period 2
Secondary outcomes (4)
Number of repetitions completed during the 30-second sit-to-stand test
Leg strength and exercise intolerance
Measured: Week 12
PROMIS Cognitive Function MELAS Short Form (PCFM-SF) score
Patient-reported questionnaire on MELAS-specific cognitive function
Measured: Week 12
Plasma concentrations of GDF-15
Measure of disease pathophysiology
Measured: Week 12
Memory composite scores (One Card Learning and One Back Tests) for Week 9 through 12
Test of memory
Measured: Week 9 through 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2024
- Study start10 Sep 2024
- Primary completion29 Jun 2026
- Study completion29 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blind, placebo-controlled, 3-treatment, 2-period, incomplete-block, 4-sequence, crossover study. Eligible patients will be randomized to 1 of 4 crossover treatment sequences. Each treatment period will last 12 weeks, separated by a 4-week washout period.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tisento Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06402123
- Sponsor's protocol ID
- TIS6463-203
- Acronym
- PRIZM
- Status last verified
- Mar 2026
- First submitted
- 2 May 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No